Department of Chemistry and Centre Pharmaqam, Université du Québec à Montréal, CP 8888, Succ. A, Montréal (Québec) H3C 3P8, Canada.
Int J Pharm. 2012 May 30;428(1-2):48-56. doi: 10.1016/j.ijpharm.2012.02.032. Epub 2012 Mar 3.
The capacity of carboxymethyl starch (CMS):Chitosan monolithic tablets to protect diamine oxidase and/or catalase therapeutic enzymes against simulated gastric fluid (SGF) and to control their delivery in simulated intestinal fluid (SIF) was investigated. Enzyme formulations loaded with grass pea seedlings diamine oxidase (PSDAO) vegetal extract, catalase, or PSDAO associated to catalase, were obtained by direct compression. The CMS:Chitosan (1:1) matrix afforded a good gastric protection to PSDAO and to catalase, when each enzyme was formulated separately. Variable amounts of DAO were delivered in the SIF containing pancreatin, with maximal release reached at about 8h, a time convenient for tablets to attain the colon. Up to 50% of the initial enzymatic activity of catalase formulated with CMS:Chitosan was found after 8 h in SIF. For the CMS:Chitosan tablets of bi-enzymatic formulations containing PSDAO:Catalase, the releases of DAO and of catalase were synchronized. The hydrogen peroxide (product of DAO activity) was decomposed by the catalase liberated in the same SIF environment. The proposed formulations could allow novel therapeutic approaches for the treatment of inflammatory bowel diseases, intestinal cancers or pseudo-allergic reactions.
羧甲基淀粉(CMS)-壳聚糖整体片剂保护二胺氧化酶和/或过氧化氢酶治疗性酶免受模拟胃液(SGF)的影响,并控制其在模拟肠液(SIF)中的释放的能力进行了研究。通过直接压缩获得了负载草豌豆幼苗二胺氧化酶(PSDAO)植物提取物、过氧化氢酶或 PSDAO 与过氧化氢酶结合的酶制剂。当每种酶单独配制时,CMS:壳聚糖(1:1)基质为 PSDAO 和过氧化氢酶提供了良好的胃保护作用。在含有胰酶的 SIF 中,以大约 8 小时达到最大释放量,这一时间方便片剂到达结肠。在 SIF 中 8 小时后,与 CMS:壳聚糖配制的过氧化氢酶的初始酶活性高达 50%。对于含有 PSDAO:过氧化氢酶的双酶制剂的 CMS:壳聚糖片剂,DAO 和过氧化氢酶的释放是同步的。在相同的 SIF 环境中释放的过氧化氢酶分解了 DAO 活性产生的过氧化氢。所提出的制剂可以为治疗炎症性肠病、肠道癌症或假性过敏反应提供新的治疗方法。